Noone, Cariosa M. and Kihm, Anthony and English, Karen and O'Dea, Shirley
(2013)
IFN-γ Stimulated Human Umbilical-Tissue-Derived
Cells Potently Suppress NK Activation
and Resist NK-Mediated Cytotoxicity In Vitro.
Stem Cells and Development, 22.
pp. 3003-3014.
ISSN 1557-8534
Abstract
Umbilical cord tissue represents a unique source of cells with potential for cell therapy applications for multiple
diseases. Human umbilical tissue-derived cells (hUTC) are a developmentally early stage, homogenous population
of cells that are HLA-ABC dim, HLA-DR negative, and lack expression of co-stimulatory molecules in the
unactivated state. The lack of HLA-DR and co-stimulatory molecule expression on unactivated hUTC may
account for their reduced immunogenicity, facilitating their use in allogeneic settings. However, such approaches
could be confounded by host innate cells such as natural killer (NK) cells. Here, we evaluate in vitro
NK cell interactions with hUTC and compare them with human mesenchymal stem cells (MSC). Our investigations
show that hUTC suppress NK activation, through prostaglandin-E2 secretion in a contact-independent
manner. Prestimulation of hUTC or human MSC with interferon gamma (IFN-g) induced expression of the
tryptophan degrading enzyme indoleamine 2, 3 dioxygenase, facilitating enhanced suppression. However,
resting NK cells of different killer immunoglobulin-like receptor haplotypes did not kill hUTC or MSC; only
activated NK cells had the ability to kill nonstimulated hUTC and, to a lesser extent, MSC. The cell killing
process involved signaling through the NKG2D receptor and the perforin/granzyme pathway; this was supported
by CD54 (ICAM-1) expression by hUTC. IFN-g-stimulated hUTC or hMSC were less susceptible to NK
killing; in this case, protection was associated with elevated HLA-ABC expression. These data delineate the
different mechanisms in a two-way interaction between NK cells and two distinct cell therapies, hUTC or hMSC,
and how these interactions may influence their clinical applications.
| Item Type: |
Article
|
| Keywords: |
stimulated human umbilical-tissue-derived cells; potently suppress NK activation; resist NK-mediated cytotoxicity; vitro; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
6843 |
| Identification Number: |
https://doi.org/10.1089/scd.2013.0028 |
| Depositing User: |
Karen English
|
| Date Deposited: |
19 Jan 2016 16:42 |
| Journal or Publication Title: |
Stem Cells and Development |
| Publisher: |
Mary Ann Liebert |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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